alpha-氨基-4-己基-2,3-二氢-3-氧代-5-异恶唑丙酸 | 334887-43-3

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: alpha-氨基-4-己基-2,3-二氢-3-氧代-5-异恶唑丙酸
• 英文名称: 2-Amino-3-(4-hexyl-3-hydroxy-isoxazol-5-yl)-propionic acid
• 英文别名: Hexylhibo；2-amino-3-(4-hexyl-3-oxo-1,2-oxazol-5-yl)propanoic acid
• CAS: 334887-43-3
• 化学式: C₁₂H₂₀N₂O₄
• 分子量: 256.302
• InChiKey: OKJBLHIYOWSQDJ-UHFFFAOYSA-N

物化性质

• 熔点：
  207-219 °C (decomp)
• 密度：
  1.176±0.06 g/cm3(Predicted)
• 溶解度：
  1eq 中可溶解至 20 mM。氢氧化钠

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-正己基乙酰乙酸甲酯 在 sodium hydroxide 、 羟胺 、 溴 、 sodium hydride 、 溶剂黄146 作用下， 以 甲醇 、 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 149.5h， 生成 alpha-氨基-4-己基-2,3-二氢-3-氧代-5-异恶唑丙酸
  参考文献：
  名称：

  Synthesis and Pharmacology of 3-Isoxazolol Amino Acids as Selective Antagonists at Group I Metabotropic Glutamic Acid Receptors

  摘要：

  Using ibotenic acid (2) as a lead, two series of 3-isoxazolol amino acid ligands for (S)-glutamic acid (Glu, 1) receptors have been developed. Whereas analogues of (RS)-2-amino-3-(3-hydroxy5-methyl-4-isoxazolyl)propionic acid [AMPA, (RS)-3] interact selectively with ionotropic Glu receptors (iGluRs), the few analogues of (RS)-2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid [HIBO, (RS)-4] so far known typically interact with iGluRs as well as metabotropic Glu receptors (mGluRs). We here report the synthesis and pharmacology of a series of 4-substituted analogues of HIBO. The hexyl analogue 9 was shown to be an antagonist at group I mGluRs. The effects of 9 were shown to reside exclusively in (S)-9 (K-b = 30 muM at mGlu(1) and K-b = 61 muM at mGlu(5)). The lower homologue of 9, compound 8, showed comparable effects at mGluRs, but 8 also was a weak agonist at the AMPA subtype of iGluRs. Like 9, the higher homologue, compound 10, did not interact with iGluRs, but 10 selectively antagonized mGlu(1) (K-b = 160 muM) showing very weak antagonist effect at mGlu(5) (K-b = 990 muM). The phenyl analogue 11 turned out to be an AMPA agonist and an antagonist at mGlu(1) and mGlu(5), and these effects were shown to originate in (S)-11 (EC50 = 395 muM, K-b = 86 and 90 muM, respectively). Compound 9, administered icy, but not sc, was shown to protect mice against convulsions induced by N-methyl-D-aspartic acid (NMDA). Compounds 9 and 11 were resolved using chiral HPLC, and the configurational assignments of the enantiomers were based on X-ray crystallographic analyses.

  DOI：

  10.1021/jm000441t

文献信息

• COMPOUNDS FOR TREATING NEUROPSYCHIATRIC CONDITIONS
  申请人：Campbell David

  公开号：US20120046283A1

  公开（公告）日：2012-02-23

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of neuropsychiatric conditions.

  本文提供了PAK抑制剂及其在治疗神经精神疾病方面的应用方法。
• 8-ETHYL-6-(ARYL)PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES FOR THE TREATMENT OF CNS DISORDERS
  申请人：Vollrath Benedikt

  公开号：US20120270866A1

  公开（公告）日：2012-10-25

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders.

  本文提供了PAK抑制剂以及利用PAK抑制剂治疗中枢神经系统疾病，如神经精神障碍的方法。
• METHODS FOR TREATING SCHIZOPHRENIA
  申请人：Lichter Jay

  公开号：US20120184547A1

  公开（公告）日：2012-07-19

  Provided herein are PAK inhibitors. Also provided herein are compositions and methods for treating an individual suffering from schizophrenia.

  提供PAK抑制剂。此外，还提供了用于治疗患有精神分裂症的个体的组合物和方法。
• 6-(SULFONYLARYL)PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES FOR THE TREATMENT OF CNS DISORDERS
  申请人：Campbell David

  公开号：US20130252966A1

  公开（公告）日：2013-09-26

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders.

  本文提供了PAK抑制剂和利用PAK抑制剂治疗中枢神经系统疾病，如神经精神疾病的方法。
• 8-(SULFONYLBENZYL)PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES FOR THE TREATMENT OF CNS DISORDERS
  申请人：Campbell David

  公开号：US20130252967A1

  公开（公告）日：2013-09-26

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders.

  本文提供了PAK抑制剂及其在治疗中枢神经系统疾病方面的应用方法。